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Treatment of interstitial cystitis

一种膀胱炎、间质性的技术，应用在抗动物/人类的免疫球蛋白、抗体、抗生长因子免疫球蛋白等方向，能够解决不能够容易地预测抗-NGF抗体等问题

Inactive Publication Date: 2011-10-12
PFIZER LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, given the etiology of IC and the poor understanding of the mechanism of the condition, it cannot be easily predicted that anti-NGF antibodies (such as antibody E3) could be used to treat patients with IC and / or Pain and / or Lower Urinary Tract Symptoms (LUTS) Associated with Painful Bladder Syndrome and / or Painful Bladder Syndrome

Method used

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  • Treatment of interstitial cystitis
  • Treatment of interstitial cystitis
  • Treatment of interstitial cystitis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0381] Example 1: Humanization and affinity maturation of mouse antagonist anti-NGF antibody 911 maturation)

[0382] A. General method

[0383] The following general method was used in this example.

[0384] library generation

[0385] As Kay et al. (1996), Phage display of peptides and proteins: a laboratory manual , San Diego, Academic Press (see pages 277-291), libraries were generated by PCR cassette mutagenesis using degenerate oligonucleotides. An amino acid position was randomized to include 20 possible amino acids using the doping codon NNK. To randomize an amino acid position to contain only a subclass of amino acids with specific properties, dopant codons are used as described in Balint et al. (1993) Gene 137(1):109-18). Site-directed mutagenesis was performed using recombinant PCR as described in Innis et al., (1990) PCR protocols: A guide to methods and applications (see pages 177-183).

[0386] Small scale Fab preparation

[0387]For screening of Fab...

Embodiment 2

[0499] Example 2: Evaluation of Anti-NGF Antibody Using Mouse E13.5 Trigeminal Neuron Survival Assay NGF-blocking ability

[0500] The ability of Fab E3 or full-length antibody E3 to block NGF activity was assessed by measuring the ability of the antibodies to inhibit NGF-dependent survival of mouse E13.5 trigeminal neurons in vitro. The trigeminal ganglion consists of epidermal sensory neurons that innervate the facial area. Survival of mouse E13.5 trigeminal neurons is a sensitive assay to evaluate the NGF-blocking activity of anti-NGF antagonist antibodies, since NGF is required to support the survival of these neurons. For example, at saturating concentrations of NGF, survival was close to 100% after 48 hours of culture. In contrast, less than 5% of neurons survived after 48 hours in the absence of NGF.

[0501] Survival experiments were performed as follows: time-mated pregnant Swiss Webster female mice were euthanized by CO2 inhalation. Uterine homs were removed a...

Embodiment 3

[0512] Example 3: Evaluation of anti-NGF antibody E3 using mouse trigeminal and tubercle neuron survival assays specificity

[0513] Antibody inhibition of mouse E17 / 18 trigeminal neuron survival in vitro was measured by measuring saturating concentrations of NGF, NGF-associated neurotrophin NT3, or NGF-independent neurotrophic factor macrophage-stimulating protein (MSP) ability to evaluate the ability of antibody E3 to specifically block NGF activity. Survival of mouse E17 / 18 trigeminal neurons is a sensitive assay for evaluating the NGF-blocking activity of anti-NGF antagonist antibodies because at higher concentrations of NGF than are required to support the survival of E13.5 TG neurons NGF is required to support the survival of these neurons. The survival of these neurons was also supported by NT3 or MSP; therefore, the survival of these neurons was also a sensitive assay to assess whether anti-NGF antagonist antibodies also blocked NT3 or MSP.

[0514] The ability o...

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Abstract

The present invention relates to the use of an anti-NGF antibody in the treatment or prevention of pain and / or a lower urinary tract symptom (LUTS) associated with interstitial cystitis and / or painful bladder syndrome and / or bladder pain syndrome.

Description

technical field [0001] The present invention relates to anti-NGF antibodies in the treatment or prevention of interstitial cystitis (interstitialcystitis) and / or painful bladder syndrome (painful bladder syndrome) and / or bladder pain syndrome (bladder pain syndrome) associated pain and / or or use in lower urinary tract symptoms (LUTS). Background technique [0002] Interstitial cystitis (IC) is a chronic bladder disorder of unknown origin characterized by symptoms of pain (eg, pelvic pain) and lower urinary tract symptoms (LUTS), such as increased urinary frequency / urgency. More recently, the term has evolved to include painful bladder syndrome (PBS) with IC (MacDiarmid SA et al., Rev Urol 2007;9(l):9-16) or bladder pain syndrome (BPS) (van der Merve et al., European Urology 53 (2008) 60-67), ie IC / PBS / BPS, collectively describe this combination of symptoms. [0003] The prevalence rate of IC / PBS / BPS ranges from 67 to 230 per 100,000 women with clinically confirmed disease,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/22A61K39/395A61P13/00
CPCC07K16/22A61K2039/505C07K2317/73C07K2317/24C07K2317/76A61P13/10A61K39/395
Inventor 艾安·威廉·密尔斯斯蒂芬·查尔斯·菲利普斯安侬·露森达尔大卫·彼得·斯科菲尔德大卫·路易斯·谢尔顿
Owner PFIZER LTD