Inhibition of NF-κB activation by blockade of...

Details Inhibition of NF-κB activation by blockade of... Inhibition of NF-κB activation by blockade of...

2005-03-08

2005-03-08

Weber, Jon (Department: 1653)

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

C530S324000, C530S329000, C514S002600, C514S012200, C514S017400

Reexamination Certificate

active

06864355

ABSTRACT:
The invention includes compositions and methods for the selective inhibition of cytokine-mediated NF-κB activation by blocking the interaction of NEMO with IκB kinase-β (IKKβ) at the NEMO binding domain (NBD). The blockade of IKKβ-NEMO interaction resulting in inhibition of IKKβ kinase activity and subsequent decreased phosphorylation of IκB. Phosphorylation of IκB being an integral step in cytokine-mediated NF-κB activation. The invention further includes methods for screening for agents capable of interacting at the NBD and therapeutic uses for such agents in pathological disorders caused by dysregulation of NF-κB activation.

REFERENCES:
patent: 5804374 (1998-09-01), Baltimore et al.
patent: 5851812 (1998-12-01), Goeddel et al.
patent: 5939302 (1999-08-01), Goeddel et al.
patent: 5972655 (1999-10-01), Marcu
patent: 6030834 (2000-02-01), Chu et al.
patent: WO 9901541 (1999-01-01), None
patent: WO 9931255-a2 (1999-06-01), None
Bower et al., “Gliocladium roseum EGIII-like cellulase”, Database A_Geneseq_032802, Accession No: AAY06332, Sep. 6, 1999.*
Cao et al., “IKK-alpha polypeptide withbinding activity” Apr. 27, 1999, Accession No. AAW96182; Database: A_Geneseq_101002.*
Adams et al., “The genome sequence ofDrosophila melanogaster”, Mar. 24, 2000; Science, vol. 287, pp. 2185-2195.*
Adams et al., “CG6060 protein”, May 1, 2000, Accession No:Q9VTL8, Database: SPTREMBL_21.*
Cole et al. “Deciphering the biology ofMycobacteium tuberculosisfrom the complete genome sequence” Jun. 11, 1998, Nature, vol. 393, pp. 537-544.*
Cole et al. “Hypothetical protein Rv2975c-Mycobacterium tuberculosis, strain H37RV” Jul. 17, 1998, Database: PIR_76, Accession No: D70672, alignment result 1, SEQ ID No:3.*
May, Michael J. et al. “Rel/NF-κB and IκB protiens: an overview.”Cancer Biology,vol. 8, pp. 63-73 (1997).
May, Michael J. et al. “Signal Transduction through NF-κB.”Immunolgy Today,vol. 19, No. 2, pp. 80-88 (1998).
Mercurio, Frank et al., “IκB Kinase (IKK)-Associated Protein 1, a Common Component of the Heterogeneous IKK Complex.” Molecular and Cellular Biology, vol. 19, No. 2, pp. 1526-1538 (1999).
Takeda, Kiyoshi et al., “Limb and Skin Abnormalities in Mice Lacking IKKα.”Science,vol. 284, pp. 313-316 (1999).
Regnier, Catherine H. et al., “Identification and Characterization of an IκB Kinase.”Cell,vol. 90, pp. 373-383 (1997).
Rothwarf, David M. et al., “IKK-γ is an essential regulatory subunit of the IκB kinase complex.”Nature,vol. 395, pp. 297-300 (1998).
Rudolph, Dorothea et al., “Severe liver degeneration and lack of NF-κB activation in NEMO/IKKγ-deficient mice.”Genes & Development,vol.14, pp. 854-862 (2000).
Siebenlist, Ulrich et al., “Structure, Regulation and Function of NF-κB.”Annu. Rev. Cell. Biol.,vol. 10, pp. 405-455 (1994).
Yamaoka, Shoji et al., “Complementation Cloning of NEMO, a Component of the IκB Kinase Complex Essential for NF-κB Activation.”Cell,vol. 93, pp. 1231-1240 (1998).
Ye, Jianjiang et al., “Regulation of the NF-κB Activation Pathway by Isolated Domains of FIP3/IKKγ, a Component of the IκB-α Kinase Complex.”The Journal of Biological Chemistry,vol. 275, No. 13, pp. 9882-9889 (2000).
Zandi, Ebrahim et al., “The IκB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKα and IKKβ, Necessary for IκB Phosphorylation and NF-κB Activation.”Cell,vol. 91, pp. 243-252 (1997).
Zhang, Si Qing et al., “Recruitment of the IKK Signalosome to the p55 TNF Receptor: RIP and A20 Bind to NEMO (IKK γ) upon Receptor Stimulation.”Immunity,vol. 12, pp: 301-311 (2000).
Zhong, Haihong et al., “The Transcriptional Activity of NF-κB Is Regulated by the IκB-Associated PKAc Subunit through a Cyclic AMP-Independent Mechanism.”Cell,vol. 89, pp. 413-424 (1997).
Britta-Mareen, E. et al., “Phosphorylation of human IκB-α on serines 32 and 36 controls IκB-α proteolysis and NF-κB activation in response to diverse stimuli.”The EMBO Journal,vol. 14, No. 12 pp. 2876-2883, (1995).
Chu, Zhi-Liang et al., “IKKγ Mediates the Interaction of Cellular IκB Kinase with the Tax Transforming protein of Human T Cell Leukemia Virus Type 1.”The Journal of Biological Chemistry,vol. 274, No. 22, pp. 15297-15300 (1999).
Delhase, Mireile et al., “Positive and Negative Regulation of IκB Kinase Activity Through IKKβ Subunit Phosphorylation .”Science,vol. 284, pp. 309-313 (1999).
DiDonato, Jospeh A. et al., “A cytokine-responsive IκB Kinase that activates the transcription factor NF-κB.”Nature,vol. 388, pp. 548-554 (1997).
DiDonato, Joseph A. et al., “Mapping of the Inducible IκB Phosphorylation Sites That Signal Its Ubiquitination and Degradation.”Molecular and Cellular Biology,vol. 16, No. 4, pp. 1295-1304 (1996)
Ghosh, Sankar et al., “NF-κB and Rel Proteins: Evolutionarily Conserved Mediators of Immune Responses.”Annu. Rev. Immunol.vol. 16, pp. 255-260 (1998).
Harhaj, Edward W. et al., “IKKγ Serves as a Docking Subunit of the IκB Kinase (IKK) and Mediates Interaction of IKK with the Human T-cell Leukemia Virus Tax Protein.”The Journal of Biological Chemistry,vol. 274, No. 33, pp. 22911-22914 (1999).
Hu, Yinling et al., “Abnormal Morphogenesis but Intact IKK Activation in Mice lacking the IKKα Subunit of IκB Kinase.”Science,vol. 284, pp. 316-320 (1999).
Kopp, Elizabeth et al., “Inhibition of NF-κB by Sodium Salicylate and Aspirin.”Science,vol. 265, pp. 956-959 (1994).
Li Qiutang et al., “Severe Liver Degeneration in Mice Lacking the IκB Kinase 2 Gene.”Science,vol. 284, pp. 321-325 (1999).
Jin, Dong-Yan et al., “Role of Adapter Function in Oncoprotein-mediated Activation of NF-κB.”The Journal of Biological Chemistry,vol. 274, No. 25, pp. 17402-17405 (1999).
Jin, Dong-Yan et al., “Isolation of Full-Length cDNA and Chromosomal Localization of Human NF-κB Modulator NEMO to Xq28.”Journal of Biomedical Science,vol. 6, pp. 115-120 (1999).
May, Michael J. et al., “Selective Inhibition of NF-κB Activation by a Peptide That Blocks the Interaciton of NEMO with the IκB Kinase Complex.”Science,vol. 289, pp. 1550-1554 (2000).

Affiliated with

Also associated with

Rating

Inhibition of NF-κB activation by blockade of... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Inhibition of NF-κB activation by blockade of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibition of NF-κB activation by blockade of... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3441442