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Interleukin-17F antibodies and other IL-17F signaling antagonists and uses therefor

1. IL-17F, IL-17F technology, applied in the field of human IL-17F and their application in regulating IL-17F-related activities, can solve the problem of not being able to target IL-17F signal transmission

Inactive Publication Date: 2011-09-14
WYETH LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, IL-17F signaling has not been targeted for disease prevention and / or treatment, although it may play a role in tissue (e.g., joint tissue) homeostasis and various diseases (e.g., arthritis, asthma, allergy, COPD, cystic fibrosis, ulcerative colitis, Crohn's disease, etc.)

Method used

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  • Interleukin-17F antibodies and other IL-17F signaling antagonists and uses therefor
  • Interleukin-17F antibodies and other IL-17F signaling antagonists and uses therefor
  • Interleukin-17F antibodies and other IL-17F signaling antagonists and uses therefor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0194] Example 1: IL-17F-mediated inflammatory response and its involvement in inflammatory disorders, such as rheumatoid arthritis, inflammatory respiratory disorders, and inflammatory bowel disease

Embodiment 11

[0195] Example 1.1: Administration of human IL-17F to mice that have not been exposed to antigen induces neutrophils to flow into the peritoneum

[0196] It was observed that IL-17F treatment resulted in increased proteoglycan decomposition and decreased proteoglycan synthesis in articular cartilage (Hymowitz et al. (2001) EMBO J. 20: 5332-41), suggesting that IL-17F signal transmission in joint tissues A role in the development of inflammatory diseases. In fact, synovial fluid samples from patients with rheumatoid arthritis and osteoarthritis exhibit degradation of proteoglycans (including, for example, aggrecan, keratin, and collagen) (see, for example, Witter et al. (1987) Arth. Rheum. 30: 519-29 and Yagi et al. (2005) J. Orthop. Res. 23(5): 1128-38), in vitro arthritis models mimic this phenomenon by displaying matrix and proteoglycan degradation (Neidhart et al. (2000) ) Arth. Rheum. 43: 1719-28).

[0197] In addition, in BAL samples isolated from patients with asthma (Kawag...

Embodiment 12

[0200] Example 1.2: IL-17F signaling plays a role in inflammatory joint disorders

[0201] In order to further evaluate the involvement of IL-17F signaling in inflammation (especially the inflammatory response involved in joint diseases (e.g., arthritis)), IL-17F activation was determined to be involved in inflammatory cytokines (ie NF-κB) in the primary generation. The ability of the basic factor of transcription in chondrocytes. Infect (100MOI) primary human or porcine chondrocytes with an adenovirus expressing the NF-κB reporter gene system, which measures the luciferase gene controlled by the NF-κB-reactive promoter To detect the activation of endogenous NF-κB (ie the translocation of NF-κB from the cytoplasm to the nucleus) (BD Mercury Pathway Profiling systems, BD Biosciences, Palo Alto, CA). After 48-72 hours, different concentrations of IL-17A (SEQ ID NO: 4) or IL-17F were used to culture the infected chondrocytes. After incubating with IL-17A or IL-17F for 4 hours, the...

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Abstract

The invention relates to the interleukin-17F antibodies and other IL-17F signaling antagonists and uses therefor. The present invention provides isolated and purified polynucleotides and polypeptides related to the IL-17F signaling pathway. The invention also provides antibodies to IL-17F homodimers and IL-17A / IL-17F heterodimers, and methods of isolating and purifying members of the IL-17 family, including IL-17A / IL-17F heterodimers, from a natural source. The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating and / or preventing disorders related to IL-17F signaling, i.e., IL-17F-associated disorders, including, but not limited to, inflammatory disorders, such as autoimmune diseases (e.g., arthritis (including rheumatoid arthritis), psoriasis, systemic lupus erythematosus, and multiple sclerosis), respiratory diseases (e.g., COPD, cystic fibrosis, asthma, allergy), transplant rejection (including solid organ transplant rejection), and inflammatory bowel diseases or disorders (IBDs, e.g., ulcerative colitis, Crohn's disease). The present invention is further directed to novel therapeutics and therapeutic targets, and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of disorders related to IL-17F signaling.

Description

[0001] This application is a divisional application of Chinese patent application 200680012523.1 "Interleukin-17F antibody and other IL-17F signaling antagonists and their uses" dated February 14, 2006. [0002] Related application [0003] This application claims the priority of U.S. Provisional Patent Application No. 60 / 653,260 filed on February 14, 2005 and U.S. Provisional Patent Application No. 60 / 667,492 filed on April 1, 2005, both of which are incorporated herein by reference in their entirety. Technical field [0004] The present invention relates to antibodies, for example, intact antibodies and antigen-binding fragments thereof, and other IL-17F signaling antagonists, for example, soluble IL-17F receptors, which interfere with interleukin-17F (IL-17F) signaling, and more Specifically, it relates to human IL-17F and their application in regulating IL-17F-related activities. The antibodies and related IL-17F molecules disclosed herein can be used for diagnosis, prognosis, m...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K45/06A61K38/20A61K39/395A61K48/00C07K16/24C07K14/54C07K1/30C07K1/22C07K19/00C12P21/00G01N33/68A61P1/00A61P11/00A61P17/06A61P19/02A61P29/00A61P37/02C12N15/113
CPCC07K16/2866C07K14/54C07K14/7155C12N15/1138C07K16/244A61K38/00A61K2039/55527A61K2039/505G01N33/6869C07K2319/30C07K2316/96C07K2317/76A61P1/00A61P1/04A61P11/00A61P11/06A61P17/06A61P19/02A61P25/00A61P29/00A61P37/00A61P37/02A61P37/06A61P43/00C07K16/24G01N33/68C07K16/28A61K39/39
Inventor B·M·卡雷尼奥M·科林斯J·F·赖特N·M·沃尔夫曼M·阿赖K·雅各布斯卢志坚郭永金邱永成
Owner WYETH LLC
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