Abstract: The invention relates to recombinant monovalent antibodies which are heterodimers of a first protein chain comprising the variable domain of the heavy chain of an antibody of interest and the CH2 and CH3 domains of an IgG immunoglobulin and a second protein chain comprising the variable domain of the light chain of said immunoglobulin of interest and the CH2 and CH3 domains of said IgG immunoglobulin. These antibodies can be used in particular as therapeutic agents in all cases where monovalent binding to a ligand such a cellular receptor is required.

Abstract: The invention relates to humanized antibodies directed against the human lymphocyte receptor CD28. When used in a monovalent form these antibodies are antagonists, i.e. capable of blocking of the CD28/B7 interaction, without activating CD28. These antibodies can be used in particular as therapeutic agents for blocking T cell activation through the CD28 receptor.

Abstract: The invention concerns antibodies directed against CD127, I.e. the alpha chain of the receptor for interleukin7 (IL-7), especially the receptor for human IL-7 expressed on human cells (designated human IL-7R alpha or IL-7Ra) or the TSLP receptor. The antibodies of the invention have cytotoxic activity against CD127 positive cells. The invention also relates to the use of these antibodies in order to deplete subpopulations of T lymphocytes as a result of cytotoxic action of the antibodies, through ADCC and optionally through CDC. Accordingly the invention concerns the use of the antibodies in the treatment of transplant rejection, autoimmune diseases, allergic diseases, lymphoma or cancer when these pathologies are associated with CD127 positive cells.

Abstract: A method of determining the non-propagation threshold of fatigue cracks at high frequency, wherein cyclic loading is exerted on at least one testpiece having an elliptical hole in a testpiece zone, the elliptical hole having a notch at one end and the testpiece being held between two rigid masses with two rigid pre-stress plates being arranged on either side of the at least one testpiece and each fastened at its two ends to the two rigid masses, which cyclic loading is at a frequency that is selected as being equal to the resonant frequency of the assembly including the testpiece, the masses, and the stress plates, so as to generate a fatigue crack from the notch, and then once it has been observed that the crack has stopped propagating, the final length of the crack is measured and a chart is used to determine the non-propagation threshold.

Abstract: A method of determining the non-propagation threshold of fatigue cracks at high frequency, wherein cyclic loading is exerted on at least one testpiece having an elliptical hole in a testpiece zone, the elliptical hole having a notch at one end and the testpiece being held between two rigid masses with two rigid pre-stress plates being arranged on either side of the at least one testpiece and each fastened at its two ends to the two rigid masses, which cyclic loading is at a frequency that is selected as being equal to the resonant frequency of the assembly including the testpiece, the masses, and the stress plates, so as to generate a fatigue crack from the notch, and then once it has been observed that the crack has stopped propagating, the final length of the crack is measured and a chart is used to determine the non-propagation threshold.

Abstract: The invention relates to humanized antibodies directed against the human lymphocyte receptor CD28. When used in a monovalent form these antibodies are antagonists, i.e. capable of blocking of the CD28/B7 interaction, without activating CD28. These antibodies can be used in particular as therapeutic agents for blocking T cell activation through the CD28 receptor.

Abstract: The invention concerns antibodies directed against CD127, I.e. the alpha chain of the receptor for interleukin7 (IL-7), especially the receptor for human IL-7 expressed on human cells (designated human IL-7R alpha or IL-7Ra) or the TSLP receptor. The antibodies of the invention have cytotoxic activity against CD127 positive cells. The invention also relates to the use of these antibodies in order to deplete subpopulations of T lymphocytes as a result of cytotoxic action of the antibodies, through ADCC and optionally through CDC. Accordingly the invention concerns the use of the antibodies in the treatment of transplant rejection, autoimmune diseases, allergic diseases, lymphoma or cancer when these pathologies are associated with CD127 positive cells.

Abstract: The invention relates to monovalent ligands of the human CD28 receptor, which can selectively block the interaction between CD28 and B7 without activating the CD28 receptor. Said ligands can be used in particular in the production of immunosuppressant drugs, selectively blocking T lymphocyte activation phenomena involving the CD28 receptor.

Abstract: The invention relates to humanized antibodies directed against the human lymphocyte receptor CD28. When used in a monovalent form these antibodies are antagonists, i.e. capable of blocking of the CD28/B7 interaction, without activating CD28. These antibodies can be used in particular as therapeutic agents for blocking T cell activation through the CD28 receptor.

Abstract: The invention relates to humanized antibodies directed against the human lymphocyte receptor CD28. When used in a monovalent form these antibodies are antagonists, i.e. capable of blocking of the CD28/B7 interaction, without activating CD28. These antibodies can be used in particular as therapeutic agents for blocking T cell activation through the CD28 receptor.

Abstract: The invention relates to monovalent ligands of the human CD28 receptor, which can selectively block the interaction between CD28 and B7 without activating the CD28 receptor. Said ligands can be used in particular in the production of immunosuppressant drugs, selectively blocking T lymphocyte activation phenomena involving the CD28 receptor.

Abstract: The invention relates to recombinant monovalent antibodies which are heterodimers of a first protein chain comprising the variable domain of the heavy chain of an antibody of interest and the CH2 and CH3 domains of an IgG immunoglobulin and a second protein chain comprising the variable domain of the light chain of said immunoglobulin of interest and the CH2 and CH3 domains of said IgG immunoglobulin. These antibodies can be used in particular as therapeutic agents in all cases where monovalent binding to a ligand such a cellular receptor is required.

Abstract: According to the invention there is provided a case (36) for storing an optical disc (38) which defines an inner region in which the optical disc is stored and includes retaining means (32, 34) disposed in the inner region for releasably retaining the optical disc in a predetermined position, wherein the case consists essentially of paper and/or cardboard and includes a paper or cardboard honeycomb portion (10).

Abstract: The invention provides 4-{[1-(aminocarbonyl)-4-piperidinyl]amino}-N-[(3,4-dimethylphenyl)methyl]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamide, which is the compound of formula (I): or a salt thereof.

Abstract: A system for interfacing with an information management tool. The system includes a memory for storing information regarding a plurality of programs, each program having at least one capability component. A processor is configured to generate a portfolio of projected capabilities by aggregating the capability components from the plurality of programs, and to create a visualization of each of the projected capabilities at discrete points in time for: analyzing an impact of each projected capability on each of the remaining projected capabilities to identify projected capability implications, and analyzing effects of reallocating resources among the programs to determine changes in the projected capability implications. The system also includes a user interface for displaying projected capability implications due to the effect of reallocating resources.

Abstract: Compounds of formula (I): wherein: R1 represents substituted or unsubstituted heteroaryl; Y represents —(CRnaRnb)n—; Rna and Rnb are each independently hydrogen or C1-6alkyl; n is an integer from 0 to 5; R2 represents unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl; R3 and R4 each independently represent hydrogen or C1-6-alkyl; R7 represents hydrogen or C1-6alkyl; R8 represents hydrogen or C1-6alkyl; and salts and solvates thereof; are CCR3 antagonists and are thus indicated to be useful in therapy.

Abstract: The invention relates to a compound of formula (I) or a salt thereof: wherein: R1 is C1-4alkyl, C1-3fluoroalkyl or —(CH2)2OH; R2 is a hydrogen atom (H), methyl or C1fluoroalkyl; R3a is a hydrogen atom (H) or C1-3alkyl; R3 is optionally substituted branched C3-6alkyl, optionally substituted C3-8cycloalkyl, optionally substituted mono-unsaturated-C5-7cycloalkenyl, optionally substituted phenyl, or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc): in which n1 and n2 independently are 1 or 2; and Y is O, S, SO2, or NR4; and wherein Het is of sub-formula (i), (ii), (iii), (iv) or (v): The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors.

Abstract: The invention relates to a compound of formula (I) or a salt thereof: wherein: R1 is Et, n-Pr, i-Pr, C2fluoroalkyl, or —CH2CH2OH; R2 is H, Me, Et, n-Pr, i-Pr, C1-2fluoroalkyl, cyclopropyl or (cyclopropyl)methyl-; and NHR3 has the sub-formula (nhr3): wherein R3a is methyl or ethyl; R3b is H, methyl or ethyl; R3c is H, methyl or ethyl, R3d is H, methyl or ethyl, and R3e is H or methyl, provided that: (a) R3b is methyl or ethyl; and/or (b) R3c and R3d are independently methyl or ethyl; and provided that: (c) when R3c is ethyl and/or when R3d is ethyl and/or when R3e is methyl, then: R3a is methyl and/or R3b is hydrogen or methyl. These compounds are PDE4 inhibitors.

Abstract: The invention provides a compound of formula (I) or a salt thereof: wherein: R1 is C1-3alkyl, C1-3fluoroalkyl, or —CH2CH2OH; R2 is hydrogen, methyl or C1fluoroalkyl; R3 is of sub-formula (aa) or (bb): wherein Y is NCONH2 and n1 is 0 or 1; R4 is H; and R5 is a group of the sub-formula (x), (y), (y1) or (z): These compounds are PDE4 inhibitors.

Abstract: The invention relates to a compound of formula (I) or a salt thereof: wherein: R1 is C1-4alkyl, C1-3fluoroalkyl, —CH2CH2OH or —CH2CH2CO2C1-2alkyl; R2 is a hydrogen atom (H), methyl or C1fluoroalkyl; R3 is optionally substituted C3-8cycloalkyl or optionally substituted mono-unsaturated-C5-7cycloalkenyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); in which n1 and n2 independently are 1 or 2; and in which Y is O, S, SO2, or NR10; or R3 is a bicyclic group (dd) or (ee): and wherein X is NR4R5 or OR5a. The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.