Abstract: Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

Abstract: Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

Abstract: The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

Abstract: The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

Abstract: Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

Abstract: The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

Abstract: A binding site in nuclear hormone receptors is described and its structural coordinates are provided. The invention provides machine-readable data storage media comprising structure coordinates of Site II and computer systems comprising the machine-readable data storage media. The invention provides methods used in the design and identification of ligands of Site II and of modulators of nuclear hormone receptors. The invention provides ligands of Site II, modulators of NHRs, pharmaceutical compositions comprising modulators of NHRs, methods of modulating NHRs, and methods of treating diseases by administering modulators of an NHR. Also provided are methods of designing mutants, mutant NHRs, Site II binding assays, and models of Site II.

Abstract: The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

Abstract: The present invention describes methods of preventing and treating inflammatory and immune-related diseases or disorders using inhibitors of I?B kinase (IKK). Also described are IKK inhibitors effective for the prevention and treatment of inflammatory and immune-related diseases or disorders, as demonstrated in vivo. Further embodiments of the present invention relate to a specific IKK inhibitors, 4(2?-aminoethyl)amino-1,8-dimethylimidazo(1,2-a) quinoxaline and compounds of formula (I), salts thereof, and pharmaceutical compositions.

Abstract: The present invention relates to polynucleotide and polypeptide sequences newly identified as associated with the NF-&kgr;B pathway. The identification of such polynucleotides and polypeptides is an important advancement toward discovering and identifying new drug targets for the treatment of NF-&kgr;B pathway-related diseases, disorders, and conditions. The invention further relates to compositions and methods for the treatment of diseases or disorders associated with the NF-&kgr;B signaling pathway using the sequences of the invention.

Abstract: The present invention provides polynucleotides encoding NF-kB-associated polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these NF-kB-associated polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

Abstract: The present invention provides a carrier for the delivery of molecules with biological function into both cellular and nuclear compartments. The carrier disclosed is heat shock protein 70 (“Hsp70”), or a fragment of Hsp70 as described herein, as a vehicle for directed, noninvasive delivery of molecules, such as proteins, peptides, or DNA, that may modulate cellular activity. The present invention also encompasses the use of Hsp70, or a fragment thereof, to modulate cellular activity, preferably to modulate nuclear activity in a cell or cells.

Abstract: The present invention is directed to polynucleotides encoding polypeptides associated with the development of osteoarthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of osteoarthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

Abstract: The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby.

Abstract: The present invention describes methods of preventing and treating inflammatory and immune-related diseases or disorders using inhibitors of I&kgr;B kinase (IKK). Also described are IKK inhibitors effective for the prevention and treatment of inflammatory and immune-related diseases or disorders, as demonstrated in vivo. Further embodiments of the present invention relate to a specific IKK inhibitors, 4(2′-aminoethyl)amino-1,8-dimethylimidazo(1,2-a) quinoxaline and compounds of formula (I), salts thereof, and pharmaceutical compositions.

Abstract: Novel compositions of immunosuppressants, such as cyclosporin, and polypeptide inhibitors of cytoplasmic protein nuclear translocation are disclosed. The compositions have, in addition to at least one immunosuppressant, at least one polypeptide inhibitor of nuclear translocation that has a signal sequence and at least one, preferably two, nuclear localization sequences. The compositions are useful as immunosuppression, antiviral and antitumor agents, preferably to prevent rejection of transplanted organs or tissue.

Abstract: Novel polypeptide inhibitors of cytoplasmic protein nuclear translocation are disclosed. The inhibitors are comprised of a signal sequence and at least two nuclear localization sequences. The polypeptides are useful as immunosuppression, antiviral and antitumor agents.