Author: claimsbot

1. A prostaglandin F2\u03b1 derivative-containing product, wherein an aqueous liquid preparation containing a prostaglandin F2\u03b1 derivative having at least a fluorine atom in its molecule is stored in a resin container made of a propyleneethylene copolymer in which the ratio of a propylene component to an ethylene component is in the range of from 94.06.0 to 99.50.5 (propylene componentethylene component), whereby a decrease in the content of the prostaglandin F2\u03b1 derivative in the aqueous liquid preparation is inhibited.
2. The prostaglandin F2\u03b1 derivative-containing product according to claim 1, wherein the prostaglandin F2\u03b1 derivative having at least a fluorine atom in its molecule is a difluoro-prostaglandin F2\u03b1 derivative.
3. The prostaglandin F2\u03b1 derivative-containing product according to claim 1, characterized in that a nonionic surfactant is contained in the aqueous liquid preparation.
4. The prostaglandin F2\u03b1 derivative-containing product according to claim 3, wherein the nonionic surfactant is polysorbate 80.
5. The prostaglandin F2\u03b1 derivative-containing product according to any one of claims 1 to 4, wherein the aqueous liquid preparation is an eye drop.
6. A method of inhibiting a decrease in the content of a prostaglandin F2\u03b1 derivative having at least a fluorine atom in its molecule in an aqueous liquid preparation, comprising storing the aqueous liquid preparation containing the prostaglandin F2\u03b1 derivative in a resin container made of a propyleneethylene copolymer in which the ratio of a propylene component to an ethylene component is in the range of from 94.06.0 to 99.50.5 (propylene componentethylene component).
7. A resin container made of a propyleneethylene copolymer in which the ratio of a propylene component to an ethylene component is in the range of from 94.06.0 to 99.50.5 (propylene componentethylene component) for storing an aqueous liquid preparation containing a prostaglandin F2\u03b1 derivative having at least a fluorine atom in its molecule.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A pump unit that can be driven by electric motor, for the generation of negative pressure for a pneumatic brake force booster, comprising a pump housing that can be closed off by a working chamber cover and comprising at least one elastic displacement element, wherein a working chamber is delimited between the displacement element and the working chamber cover, and said working chamber is assigned in each case inlet and outlet valves and inlet and outlet ducts assigned to the valves, and means for reducing an area of contact between the working chamber cover and the pump housing.
2. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the means are in the form of at least three molded protuberances distributed over the circumference of a housing flange, such that a spatially stable support is realized between the working chamber cover and the pump housing.
3. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the working chamber cover has a top cover and a bottom cover with a lower bottom cover flange, and the means are in the form of at least three molded protuberances distributed over the circumference of the lower bottom cover flange, such that a spatially stable support is realized between the working chamber cover and the pump housing.
4. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the working chamber cover has a top cover with a top cover flange and has a bottom cover with an upper bottom cover flange, wherein means for reducing a mutual area of contact are provided between the top cover and the bottom cover.
5. The pump unit that can be driven by electric motor as claimed in claim 4, wherein the means are in the form of at least three molded protuberances distributed over the circumference of the top cover flange or of the upper bottom cover flange, such that a spatially stable support is realized between the top cover and the bottom cover.
6. The pump unit that can be driven by electric motor as claimed in claim 2, wherein the working chamber cover is separated from the pump housing, andor the top cover is separated from the bottom cover, by at least one elastic decoupling element for the purpose of reducing a transmission of vibrations.
7. The pump unit that can be driven by electric motor as claimed in claim 6, wherein the elastic decoupling element is connected to at least one seal element to form a gasket.
8. The pump unit that can be driven by electric motor as claimed in claim 1, wherein at least one insert part that can be loaded in a valve opening direction by a valve plate is arranged, so as to be secured against rotation, in the inlet or the outlet duct.
9. The pump unit that can be driven by electric motor as claimed in claim 8, wherein the insert part has means for locking the insert part in corresponding locking openings, wherein the locking openings are provided in the bottom cover.
10. The pump unit that can be driven by electric motor as claimed in claim 8, wherein the insert part has at least one impact surface, which is rounded in a valve opening direction, for the abutment of the valve plate during the valve opening process.
11. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the bottom cover has a valve support surface for the support of the valve plate in a closed valve state, wherein at least one recess for reducing an area of contact between the valve plate and the valve support surface is arranged in the valve support surface.
12. A pump unit that can be driven by electric motor, for the generation of negative pressure for a pneumatic brake force booster, comprising a pump housing that can be closed off by a working chamber cover and comprising at least one elastic displacement element, wherein the working chamber cover has a top cover and a bottom cover, and wherein a working chamber is delimited between the displacement element and the working chamber cover, and said working chamber is assigned in each case inlet and outlet valves and inlet and outlet ducts assigned to the valves, wherein the inlet and outlet ducts are at least partially surrounded by the top cover, and a length of an outer contour of the top cover is significantly smaller than a length of an outer contour of the bottom cover.
13. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the pump unit can be fastened in elastically vibration-decoupled fashion in a base holder, wherein the elastic decoupling is realized by damping elements, wherein the base holder has supporting elements for receiving damping elements, and wherein at least one supporting element is manufactured by deformation of the base holder.
14. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the pump unit can be fastened in elastically vibration-decoupled fashion in a base holder, wherein the elastic decoupling is realized by damping elements, wherein at least one of the damping elements has an inner shell with a conical inner contour and an outer shell, wherein the inner shell by an encircling collar and by radial webs arranged at least on one side of the collar.
15. The pump unit that can be driven by electric motor as claimed in claim 1, wherein an air outlet unit, which is pneumatically connected to the outlet duct, for the discharge of the air into the surroundings of the pump unit is provided, wherein the air outlet unit has an intermediate base with at least one passage opening, wherein the intermediate base comprises means closing the passage openings, in water-tight fashion in the direction of the outlet duct, in the manner of a check valve.
16. The pump unit that can be driven by electric motor as claimed in claim 15, wherein the means for closing passage openings are in the form of an elastically resilient tab that is integrally formed on the intermediate base.
17. The pump unit that can be driven by electric motor as claimed in claim 1, wherein an air outlet unit, which is pneumatically connected to the outlet duct, for the discharge of the air into the surroundings of the pump unit is provided, wherein the air outlet unit has a check valve with an elastic valve disk, and the check valve closes pneumatically in the direction of the outlet duct, wherein the valve disk is loaded counter to the valve opening direction by an elastic element.
18. The pump unit that can be driven by electric motor as claimed in claim 17, wherein a disk element is provided so as to be arranged between the elastic element and the valve disk.
19. The pump unit that can be driven by electric motor as claimed in claim 17, wherein the elastic element is in the form of a spiral spring.
20. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the pump unit is driven by an electric drive unit, wherein at least two elastic intermediate elements are interposed, so as to act in parallel, between the pump housing and the drive unit, wherein an inner intermediate element is provided for pneumatic and hydraulic sealing with respect to the surroundings of the pump unit, and an outer intermediate element is provided for a vibration decoupling of the drive unit from the pump housing, and wherein the intermediate elements are connected to one another by at least two elastic connecting webs.
21. The pump unit that can be driven by electric motor as claimed in claim 1, wherein the displacement element has an elastic diaphragm element and a connecting rod element, wherein the diaphragm element is non-detachably connected to the connecting rod element by an insert molding process, wherein the connecting rod element is of unipartite form and has a shank part and a connecting rod ring part.
22. The pump unit that can be driven by electric motor as claimed in claim 12, wherein the pump unit can be fastened in elastically vibration-decoupled fashion in a base holder, wherein the elastic decoupling is realized by means of damping elements, wherein the base holder has supporting elements for receiving damping elements, and wherein at least one supporting element is manufactured by deformation of the base holder.
23. The pump unit that can be driven by electric motor as claimed in claim 12, wherein the pump unit can be fastened in elastically vibration-decoupled fashion in a base holder, wherein the elastic decoupling is realized by damping elements, wherein at least one of the damping elements has an inner shell with a conical inner contour and an outer shell, wherein the inner shell is connected to the outer shell by an encircling collar and by radial webs arranged at least on one side of the collar.
24. The pump unit that can be driven by electric motor as claimed in claim 12, wherein an air outlet unit, which is pneumatically connected to the outlet duct, for the discharge of the air into the surroundings of the pump unit is provided, wherein the air outlet unit has an intermediate base with at least one passage opening, wherein the intermediate base comprises means closing the passage openings, in water-tight fashion in the direction of the outlet duct, in the manner of a check valve.
25. The pump unit that can be driven by electric motor as claimed in claim 12, wherein an air outlet unit, which is pneumatically connected to the outlet duct, for the discharge of the air into the surroundings of the pump unit is provided, wherein the air outlet unit has a check valve with an elastic valve disk, and the check valve closes pneumatically in the direction of the outlet duct, characterized in that the valve disk is loaded counter to the valve opening direction by an elastic element.
26. The pump unit that can be driven by electric motor as claimed in claim 12, wherein the pump unit is driven by an electric drive unit, characterized in that at least two elastic intermediate elements are interposed, so as to act in parallel, between the pump housing and the drive unit, wherein an inner intermediate element is provided for pneumatic and hydraulic sealing with respect to the surroundings of the pump unit, and an outer intermediate element is provided for a vibration decoupling of the drive unit from the pump housing, and wherein the intermediate elements are connected to one another by at least two elastic connecting webs.
27. The pump unit that can be driven by electric motor as claimed in claim 12, wherein the displacement element has an elastic diaphragm element and a connecting rod element, wherein the diaphragm element is non-detachably connected to the connecting rod element by an insert molding process, wherein the connecting rod element is of unipartite form and has a shank part and a connecting rod ring part.

1. A biocompatible composition for treating, repairing, or replacing biological tissue comprising microspheres of a biodegradable polymer dispersed in a matrix of a non-biodegradable hydrogel, wherein the composition is formulated to have compatible mechanical properties and physical functionality with the biological tissue.
2. A composition according to claim 1, wherein upon biodegradation, the microspheres form open-celled pores.
3. A composition according to claim 1 where the composition has pre-existing pores throughout its structure.
4. A composition according to claim 1, wherein the non-biodegradable hydrogel is polyvinyl alcohol.
5. A composition according to claim 1, wherein the non-biodegradable hydrogel is polyvinyl alcohol and polyvinylpyrrolidone.
6. A composition according to claim 1, wherein the biodegradable polymer is poly lactic glycolic acid.
7. A composition according to claim 6, wherein the mole ratio of lactic to glycolic acid is about 50:50.
8. A composition according to claim 1, wherein the hydrogel further comprises a chemoattractant, chemokine, cytokine, adhesion molecules, or mixtures thereof.
9. A composition according to claim 1, wherein the microspheres further comprise a chemoattractant, chemokine, cytokine, adhesion molecules, or mixtures thereof.
10. A composition according to claim 9, wherein the chemoattractant is selected from the group consisting of IGF-1, FGF, BMP2, and mixtures thereof.
11. A composition according to claim 9, wherein the chemoattractant promotes the biosynthesis of extracellular-matrix.
12. A composition according to claim 9, wherein the type and amount of chemokine is compatable with the biological tissue.
13. A composition according to claim 1, wherein the microspheres have an average diameter between about 10 and about 100 microns.
14. A composition according to claim 1, wherein the composition is molded in the shape of a biological tissue defect.
15. A composition according to claim 1, wherein the composition is molded in the shape of a cylinder, cone, or ovoid for insertion into a biological tissue defect.
16. A composition according to claim 1, wherein the biological tissue is selected from the group consisting of cartilage, bone, bladder, liver, kidney, and mixtures thereof.
17. A composition according to claim 1, wherein the microspheres are unevenly dispersed in the matrix to form pores, avenues, or channels upon degradation.
18. A composition according to claim 17, wherein the pores, avenues, or channels formed upon degradation are sufficiently large to permit cellular migration into the remaining matrix of non-biodegradable hydrogel.
19. A composition according to claim 1, wherein the microspheres of biodegradable polymer are selected to degrade in vivo at a rate such that mechanical and functional characteristics of the implanted composition are maintained by the simultaneous ingrowth of biological material.
20. The composition according to claim 1, wherein the composition contains two or more discreet layers, wherein each layer has compatible mechanical properties and physical functionality for a distinct biological tissue.
21. The composition according to claim 20, wherein the composition has two layers, and further wherein one layer is compatible with bone and one layer is compatible with cartilage.
22. A method of making a composition according to claim 1, comprising forming microspheres containing a chemokine, dispersing the microspheres in a hydrogel matrix, and molding the matrix in the form of a biological tissue defect.
23. A method of treating, repairing, or replacing biological tissue comprising administering a composition according to claim 1 to a site of treatment, repair, or replacement in a patient.
24. The method of claim 23 wherein the biological tissue is selected from the group consisting of cartilage, bone, bladder, liver, kidney, and mixtures thereof.
25. A method of providing mechanical integrity to a biological defect comprising implanting a composition according to claim 1 to the site of a biological defect and allowing tissue ingrowth within biodegradable pores of the implanted composition, wherein the implanted composition provides mechanical integrity before, during, and after tissue ingrowth.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

What is claimed is:

1. A polypeptide comprising a single-domain of the variable region of the heavy chain of an antibody molecule, which is soluble and stable and capable of binding a specific antigen of interest, said polypeptide comprising a natural framework scaffold of a mammalian monoclonal antibody without induced mutations or modifications in the original VHVL interface framework residues, said VHVL interface comprising at least one charged residue.
2. The polypeptide of claim 1 wherein the polypeptide is substantially monomeric.
3. The polypeptide of claim 1, wherein the polypeptide is encoded by a polynucleotide isolated from a phage clone selected from a phage-display library comprising a plurality of recombinant phage, each of said recombinant phages having an expression vector encoding a single-domain of the variable region of the heavy chain of an antibody molecule comprising a natural framework scaffold of a mammalian monoclonal antibody without induced mutations or modifications in the original VHVL interface framework residues, having a unique VHVL interface comprising at least one charged residue and a randomized CDR3.
4. The polypeptide of claim 3 wherein the selected clone is produced in E. coli as insoluble inclusion bodies and the isolated polypeptide is subsequently refolded in-vitro and purified.
5. The polypeptide claim 3 wherein the scaffold element representing the VHVL interface comprises the sequence Lysine-44, Leucine-45, and Tryptophan-47.
6. The polypeptide of claim 1 wherein the specific antigen of interest is an immunoglobulin molecule.
7. The polypeptide of claim 3 wherein the CDR3 sequence between residues 95 and 100 C comprises the consensus sequence: Gly-X-Ser-Pro-Gln, wherein X represents any amino acid.
8. The polypeptide of claim 3 wherein the CDR3 sequence between residues 95 and 100 C is selected from the sequences: Gln-Ser-Gly-Gln-Ser-Pro-Gln-Ser-Ile, and Asn-Gly-Lys-Ser-Pro-Gln-Ala-Ala-Trp.
9. The polypeptide of claim 1 wherein the specific antigen of interest is tumor necrosis factor.
10. The polypeptide of claim 9 wherein the CDR3 sequence between residues 95 and 100 C comprises the sequence: Phe-Pro-Thr-Gly-Asp-Leu-Ala-Glu-Lys.
11. The polypeptide of claim 1 wherein the specific antigen of interest is Streptavidin.
12. The polypeptide of claim 11 wherein the CDR3 sequence between residues 95 and 100 C is selected from the sequences: His-Ala-Gln-Arg-Arg-Pro-Trp-Ile-Arg, and Glu-Asp-Pro-His-Pro-Gln-Arg-Gly-Tyr.
13. A peptide capable of binding a specific antigen of interest, said peptide being derived from the randomized sequence of the CDR3 region of a polypeptide comprising a single-domain of the variable region of the heavy chain of an antibody molecule, which is soluble and stable and capable of binding said specific antigen of interest, said polypeptide comprising a natural framework scaffold of a mammalian monoclonal antibody without induced mutations or modifications in the original VHVL interface framework residues, said VHVL interface comprising at least one charged residue.
14. The peptide of claim 13 wherein the polypeptide is encoded by a polynucleotide isolated from a phage clone selected from a phage-display library comprising a plurality of recombinant phage, each of said recombinant phages having an expression vector encoding a single-domain of the variable region of the heavy chain of an antibody molecule comprising a natural framework scaffold of a mammalian monoclonal antibody without induced mutations or modifications in the original VHVL interface framework residues, having a unique VHVL interface comprising at least one charged residue and a randomized CDR3.
15. The peptide of claim 13 wherein the peptide comprises 4-20 amino acids.
16. The peptide of claim 13 wherein the peptide comprises 7-15 amino acids.
17. The peptide of claim 13 wherein the specific antigen of interest is an immunoglobulin molecule.
18. The peptide of claim 13 wherein the specific antigen of interest is tumor necrosis factor.
19. A pharmaceutical composition comprising as an active ingredient the polypeptide of claim 1, and a physiologically acceptable diluent or carrier.
20. A pharmaceutical composition comprising as an active ingredient the peptide of claim 13, and a physiologically acceptable diluent or carrier.
21. A phage-display library comprising a plurality of recombinant phage, each of said recombinant phage having an expression vector encoding a single-domain of the variable region of the heavy chain of an antibody molecule comprising a natural framework scaffold of a mammalian monoclonal antibody without any mutations or modifications in the original interface framework residues, having a unique VHVL interface comprising at least one charged residue, and a randomized CDR3.
22. The phage display library of claim 21 wherein the single-domain variable region of the heavy chain is substantially monomeric.
23. The phage display library of claim 21 wherein the scaffold element representing the VHVL interface comprises the sequence Lysine-44, Leucine-45, and Tryptophan-47.
24. An isolated phage clone which binds selectively to a specific antigen of interest, said clone being selected from a phage-display library comprising a plurality of recombinant phage, each of said recombinant phage having an expression vector encoding a single-domain of the variable region of the heavy chain of an antibody molecule comprising a natural framework scaffold of a mammalian monoclonal antibody without any mutations or modifications in the original interface framework residues, having a unique VHVL interface and a randomized CDR3.
25. The isolated phage clone of claim 24 wherein the phage display library comprises a scaffold element representing the VHVL interface comprising the sequence Lysine-44, Leucine-45, and Tryptophan-47.
26. The isolated phage clone of claim 24 encoding a polypeptide wherein the specific antigen of interest is an immunoglobulin molecule.
27. The isolated phage clone of claim 24 encoding a polypeptide wherein the specific antigen of interest is tumor necrosis factor.
28. A method of treatment of a disease comprising administering to a patient in need thereof a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of the polypeptide of claim 1.
29. A method of diagnosis of a disease comprising administering to a patient in need thereof a pharmaceutical composition comprising as an active ingredient the polypeptide of claim 1 in an amount which is effective to diagnose the disease.
30. A method of treatment of a disease comprising administering to a patient in need thereof a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of the polypeptide of claim 13.
31. A method of diagnosis of a disease comprising administering to a patient in need thereof a pharmaceutical composition comprising as an active ingredient the polypeptide of claim 13 in an amount which is effective to diagnose the disease.
32. A method of treatment of a disease comprising administering to a patient in need thereof a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of the polypeptide of claim 9.
33. A method of diagnosis of a disease comprising administering to a patient in need thereof a pharmaceutical composition comprising as an active ingredient the polypeptide of claim 9 in an amount which is effective to diagnose the disease.