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Methods for treating post-surgical pain by admisnistering a nerve growth factor antagonist and compositions containing the same

A technology of nerve growth factor and postoperative pain, which is applied in the field of prevention, improvement or treatment of postoperative pain, and can solve the problems of not very effective pain, limited therapeutic use, sedation tolerance and addiction, etc.

Inactive Publication Date: 2006-01-18
RINAT NEUROSCI CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The first category includes nonsteroidal anti-inflammatory drugs (NSAIDs), which can be used to treat mild or moderate pain, but their therapeutic use is limited by adverse gastrointestinal effects such as gastric erosion, peptic ulcer formation or duodenal and inflammation of the colon
Long-term use of NSAIDs can also cause nephrotoxicity and, in addition, as described below, are not very effective in the treatment of pain associated with or caused by certain conditions, including postoperative pain
The second category includes morphine and related opioids, which are indicated for the treatment of moderate to severe pain, but whose therapeutic use is limited by adverse effects such as sedation, confusion, constipation, respiratory depression, renal colic, tolerance to dangers of addiction and addiction
Also, this cannot be reversed by local injection of anesthetic after cutting

Method used

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  • Methods for treating post-surgical pain by admisnistering a nerve growth factor antagonist and compositions containing the same
  • Methods for treating post-surgical pain by admisnistering a nerve growth factor antagonist and compositions containing the same
  • Methods for treating post-surgical pain by admisnistering a nerve growth factor antagonist and compositions containing the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0191] Anti-NGF monoclonal antibody is effective in treating postoperative pain

[0192] We evaluated the therapeutic efficacy of anti-NGF antibody 911 (mouse monoclonal antibody; see Hongo et al., Hybridoma 19:215-227 (2000)) using a pain model simulating postoperative pain. Each experiment included 16 animals (n=8 15 hours before cutting, the anti-NGF antibody was injected intraperitoneally (i.p.), for each test, the concentration of the antibody was different (35 or 7 mg / kg). The control group did not receive the antibody, but the intraperitoneal Saline solution is injected.

[0193] animal. Male Sprague Dawley rats weighing 220-240 grams were purchased from Harlan (San Diego) and allowed to acclimatize in the animal house for one week prior to surgery.

[0194] Operation. Surgery was performed according to the procedure disclosed by Brennan, et al., Pain 64:493-501 (1996). Animals were anesthetized with 2% isoflurane in air mixture and maintained via nose co...

Embodiment 2

[0200] Treatment of postoperative pain with humanized anti-NGF antibody and opioid therapy for postoperative pain

[0201] treatment comparison

[0202] The effect of a humanized anti-NGF antibody designated E3 on postoperative pain was examined in the animal model for postoperative pain as described in Example 1. The E3 antibody includes a human heavy chain IgG2a constant region (which contains the following mutations: A330P331 to S330S331 (amino acid numbering refers to the wild-type IgG2a sequence; see Eur. J. Immunol. (1999) 29:2613-2624)); human light chain kappa constant region; and heavy and light chain variable regions, as shown in Tables 1 and 2.

[0203] Anti-NGF antibodies were injected intraperitoneally (i.p.) at various antibody concentrations (0.004, 0.01, 0.02, 0.1, 0.6 and 1 mg / kg animal body weight) 15 hours before incision. The negative control group received no antibody and was injected intraperitoneally with saline solution. Twenty-...

Embodiment 3

[0206] Preoperative and postoperative treatment of postoperative pain with anti-NGF antibodies

[0207] The efficacy of anti-NGF antibodies in reducing postoperative pain was tested in the animal model of postoperative pain described in Example 1 using male Sprague Dawley rats purchased from Harlan (Wisconsin), when administered after incision. Two hours after making the incision, humanized anti-NGF antibody E3 (0.5 mg / kg) was injected intravenously (i.v.). A control group received no antibody and received saline solution intravenously. Surgery was performed as described in Example 1, and rest pain was assessed as cumulative pain scores 24 hours after surgery. Such as Figure 5 As shown, treatment with anti-NGF antibody significantly reduced rest pain 24 hours after incision when the antibody was administered 2 hours after incision (p<0.05). These results demonstrate that anti-NGF is effective in improving postoperative pain when administered postoperatively.

[0208...

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Abstract

The invention features methods and compositions for preventing or treating pain resulting from surgery or an incision by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as anti-hNGF) antibody that is capable of binding hNGF.

Description

[0001] Cross references to related applications [0002] This application claims the benefit of priority to US Provisional Patent Application Serial No. 60 / 417,237, filed October 8, 2002, the contents of which are incorporated by reference in their entirety. [0003] Statement Regarding Federally Sponsored Research or Development [0004] This invention was made with United States Government support through DARPA under Contract No. DAAD19-03-C-0006. The US Government may have certain rights in this invention. field of invention [0005] The invention relates to the use of a nerve growth factor (NGF) antagonist for preventing, improving or treating postoperative pain. Background of the invention [0006] Nerve growth factor (NGF) was the first identified neurotrophin and its role in the development and survival of peripheral and central neurons has been well characterized. NGF has been shown to be a crit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395G01N33/53C07K16/22C07K16/28
CPCC07K16/22A61K2039/505C07K2317/24A61P25/04A61P29/00A61P41/00A61P43/00A61K39/395G01N33/53
Inventor D·L·谢尔顿G·J·韦尔加拉
Owner RINAT NEUROSCI CORP
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