Abstract: This invention relates to IL-9 muteins that inhibit the activity of wild-type IL-9, multimers and Fc-fusion constructs of IL-9 proteins, and an efficient method to purify IL-9 proteins produced by eukaryotic cells. Related formulations, dosages and methods of administration thereof for therapeutic purposes are also provided. More particularly, these IL-9 muteins, compositions, and methods provide a treatment option for individuals afflicted with conditions where inhibiting IL-9 mediated immune responses would be beneficial, such as allergy, asthma, chronic obstructive pulmonary disease (emphysema and chronic bronchitis), pulmonary and gastro-intestinal mucus hyperplasia, inflammation, immunological disorders, leukemia, and lymphoma.

Abstract: This invention provides novel peptides that function in vivo to stimulate insulin release from pancreatic beta cells in a glucose-dependent fashion. These insulin secretagogue peptides are shown to stimulate insulin release in rat islet cells in vitro, and in vivo. The peptides of the present invention provide a new therapy for patients with decreased endogenous insulin secretion, in particular type 2 diabetics. In particular, the invention is a polypeptide selected from a specific group of VIP/PACAP-related polypeptides, or functional equivalents thereof. The invention is also directed to a method of treating a metabolic disease in a mammal comprising administering a therapeutically effective amount of the insulin secretagogue peptides to said mammal. Also disclosed are methods of making the peptides, both recombinant and synthetic.

Abstract: This invention relates to IL-9 muteins that inhibit the activity of wild-type IL-9, multimers and Fc-fusion constructs of IL-9 proteins, and an efficient method to purify IL-9 proteins produced by eukaryotic cells. Related formulations, dosages and methods of administration thereof for therapeutic purposes are also provided. More particularly, these IL-9 muteins, compositions, and methods provide a treatment option for individuals afflicted with conditions where inhibiting IL-9 mediated immune responses would be beneficial, such as allergy, asthma, chronic obstructive pulmonary disease (emphysema and chronic bronchitis), pulmonary and gastro-intestinal mucus hyperplasia, inflammation, immunological disorders, leukemia, and lymphoma.

Abstract: The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

Abstract: This invention provides novel peptides that function in vivo to stimulate insulin release from pancreatic beta cells in a glucose-dependent fashion. These insulin secretagogue peptides are shown to stimulate insulin release in rat islet cells in vitro, and in vivo. The peptides of the present invention provide a new therapy for patients with decreased endogenous insulin secretion, in particular type 2 diabetics. In particular, the invention is a polypeptide selected from a specific group of VIP/PACAP-related polypeptides, or functional equivalents thereof. The invention is also directed to a method of treating a metabolic disease in a mammal comprising administering a therapeutically effective amount of the insulin secretagogue peptides to said mammal. Also disclosed are methods of making the peptides, both recombinant and synthetic.

Abstract: The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

Abstract: A method of treating particles to be used in immunoassays reduces interference in particle agglutination assays. For particles having covalently bound antibodies and residual NHS-ester or sNHS-ester groups on the surface, the reactive esters are treated with an aqueous mixture containing an amine compound of formula (I): H2N—R—X??(I). The moiety —X is —NH2, —OH, or —CO2CH2CH3; and R is an alkyl group or an alkyl ether group. When —X is —NH2 or —CO2CH2CH3, R contains from 1 to 20 carbon atoms; and when —X is —OH, R contains from 4 to 20 carbon atoms.

Abstract: This invention relates to IL-9 muteins that inhibit the activity of wild-type IL-9, multimers and Fc-fusion constructs of IL-9 proteins, and an efficient method to purify IL-9 proteins produced by eukaryotic cells. Related formulations, dosages and methods of administration thereof for therapeutic purposes are also provided. More particularly, these IL-9 muteins, compositions, and methods provide a treatment option for individuals afflicted with conditions where inhibiting IL-9 mediated immune responses would be beneficial, such as allergy, asthma, chronic obstructive pulmonary disease (emphysema and chronic bronchitis), pulmonary and gastro-intestinal mucus hyperplasia, inflammation, immunological disorders, leukemia, and lymphoma.

Abstract: The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

Abstract: A reagent for use in immunoassays reduces interference in particle agglutination assays. The reagent contains particles having covalently bound antibodies and a tertiary amine compound of formula (I): N(R1—X)(R2—Y)(R3—Z)  (I). The moieties R1, R2, and R3 are independently alkyl or alkyl ether. The moieties X, Y, and Z are independently —OH, —O—R4, —S—R4, —C(═O)—OH, —C(═O)—OR4, or —C(═O)—NHR4 (R4 is alkyl).

Abstract: A reagent for use in immunoassays reduces interference in particle agglutination assays.

Abstract: A method of treating particles to be used in immunoassays reduces interference in particle agglutination assays.

Abstract: A method of treating particles to be used in immunoassays reduces interference in particle agglutination assays.

Abstract: This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of interleukin 4. Further, the invention is directed to IL-4 muteins having single and double mutations represented by the designators R121E and T13D/R121E, numbered in accordance with wild type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

Abstract: The invention is directed to human IL-4 muteins numbered in accordance with wild-type IL-4 having T cell activating activity, but having reduced endothelial cell activating activity. In particular, the invention is related to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. Further, the invention is directed to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R121I, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild type IL-4 (His=1).

Abstract: This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of interleukin 4. Further, the invention is directed to IL-4 muteins having single and double mutations represented by the designators R121E and T13D/R121E, numbered in accordance with wild type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

Abstract: A recombinant human IL-4 mutein numbered in accordance with wild-type IL-4 wherein the mutein comprises at least one amino acid substitution in the binding surface of either the A- or C-alpha helices of the wild-type IL-4 whereby the mutein binds to the IL-4R&agr; receptor with at least greater affinity than native IL-4. The substitution is more preferably selected from the group of positions consisting of, in the A-helix, positions 13 and 16, and in the C-helix, positions 81 and 89. A most preferred embodiment is the recombinant human IL-4 mutein wherein the substitution at position 13 is Thr to Asp. Pharmaceutical compositions, amino acid and polynucleotide sequences encoding the muteins, transformed host cells, antibodies to the muteins, and methods of treatment are also described.

Abstract: This invention is directed to recombinant human IL-4 muteins numbered in accordance with wild-type IL-4 wherein the muteins comprise at least one amino acid substitution selected from the group consisting of substitutions at positions 13, 16, 81 and 89 of the wild-type IL-4, whereby the mutein binds to the IL-4R.alpha. receptor with at least greater affinity than native IL-4. The invention is further directed to recombinant human IL-4 antagonist muteins numbered in accordance with wild-type IL-4 wherein the muteins comprise substitutions R121D and Y124D in the D-helix of said wild-type IL-4; and at least one amino acid substitution selected from the group consisting of substitutions at positions 13, 16, 81 and 89 of said wild-type IL-4, whereby the mutein binds to the IL-4R.alpha. receptor with at least greater affinity than native IL-4. The invention is also directed to pharmaceutical compositions comprising individual muteins in combination with pharmaceutically acceptable carriers.

Abstract: The invention is directed to human IL-4 muteins numbered in accordance with wild-type IL-4 having T cell activating activity, but having reduced endothelial cell activating activity. In particular, the invention is related to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. Further, the invention is directed to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R1211, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild type IL-4 (His=1).

Abstract: Methods are disclosed for conducting assays. One such method comprises providing in combination a first bibulous member zone ("first zone") and a liquid medium containing a component. The first zone has non-diffusively bound thereto a reagent interreactive with the component. Conditions are selected wherein the liquid medium and at least a portion of the component contained therein traverse all of the first zone and migrate by capillary migration into a second bibulous member zone ("second zone"). The second zone is of a different composition than the first zone and is incapable of specifically binding the component except when an analyte is to be detected and the method further includes causing a reagent to become bound to the first bibulous member zone in relation to the amount of analyte present.