Author: claimsbot

1. A work station for assembling multiple tire components onto a tire building drum having an axis of rotation; comprising:
a first set of measuring drums;
a second set of measuring drums;
lateral motion means for independently and controllably moving the first and second sets of measuring drums, respectively, in a direction parallel to the axis of rotation of the building drum; and
longitudinal motion means for independently and controllably moving the first and second sets of measuring drums in a direction perpendicular to the axis of rotation of the building drum,
wherein the first set of measuring drums are positioned laterally inside of the second set of measuring drums and the second set of measuring drums are movable towards the tire building drum so as to pass laterally outside of and around the first set of measuring drums.
2. A work station according to claim 1, including:
a first set of measuring drum carriages for the first set of measuring drums;
a second set of measuring drum carriages for the second set of measuring drums;
a first set of drum support bases for attaching the first set of measuring drums to the first set of measuring drum carriages;
a second set of drum support bases for attaching the second set of measuring drums to the second set of measuring drum carriages.
3. A work station according to claim 2, wherein:
the first set of measuring drum carriages associated with the first set of measuring drums are positioned laterally inside of the second set of measuring drum carriages associated with the second set of measuring drums.
4. A work station according to claim 2, wherein:
the lateral motion means comprise laterally oriented leadscrews and lateral leadscrew followers, with both the first and second measuring drum carriages connected to a lateral leadscrew follower.
5. A work station according to claim 2, wherein:
the longitudinal motion means comprise a longitudinally oriented leadscrew mounted to each of the first and second sets of measuring drum carriages and a longitudinal leadscrew follower associated with each longitudinally oriented leadscrew, each of the first and second sets of measuring drum support bases being connected to a longitudinal leadscrew follower.

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. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH alpha subunit by the mutation F17T.
2. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH alpha subunit by the mutation E56N.
3. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutation A70N.
4. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutation V78N.
5. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutation G100N.
6. An isolated mutant of human Follicle Stimulating Hormone (FSH) mutant having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutations D41NA43T.
7. A composition comprising the FSH mutant according to any one of claims 1-6 and at least one pharmaceutically acceptable carrier or excipient.
8. A method of treating an infertile human, comprising administering to the human in need thereof an effective amount of the human FSH mutant according to any one of claims 1-6.
9. A method of stimulating folliculogenesis in a human, comprising administering to the human an effective amount of the FSH mutant according to any one of claims 1-6.
10. A method of inducing ovarian hyperstimulation in a human, comprising administering to the human an effective amount of the FSH mutant according to any one of claims 1-6.
11. An isolated nucleic acid encoding the FSH mutant of claim 1.
12. An isolated nucleic acid encoding the FSH mutant of claim 2.
13. An isolated nucleic acid encoding the FSH mutant of claim 3.
14. An isolated nucleic acid encoding the FSH mutant of claim 4.
15. An isolated nucleic acid encoding the FSH mutant of claim 5.
16. An isolated nucleic acid encoding the FSH mutant of claim 6.
17. An expression vector comprising the nucleic acid according to any one of claims 11-16.
18. An isolated host cell transformed with a vector according to claim 17.
19. The isolated host cell of claim 18 which is eukaryotic.
20. The isolated host cell of claim 19 which is mammalian.
21. A method for producing a FSH mutant, comprising subjecting the isolated host cell according to claim 18 to cultivation under conditions conducive for expression of the FSH mutant to thereby produce the FSH mutant.
22. A method for producing a FSH mutant, comprising subjecting the isolated host cell according to claim 19 to cultivation under conditions conducive for expression of the FSH mutant to thereby produce the FSH mutant.
23. A method for producing a FSH mutant, comprising subjecting the isolated host cell according to claim 20 to cultivation under conditions conducive for expression of the FSH mutant to thereby produce the FSH mutant.

1. A compound according to the formula
AGZW
or a pharmaceutically acceptable salt, solvates or hydrate thereof, wherein
A is (C6-C10)aryl, (C6-C10)aryl-SO2, (C6-C10)aryl-CH2, (C6-C10)arylcarbonyl, (C1-C9)heteroaryl, (C1-C9)heteroaryl-SO2, (C1-C9)heteroaryl-CH2; or (C1-C9)heteroarylcarbonyl;
G is:
33
where B is (C6-C10)aryl or (C1-C9)heteroaryl, and X is CH2, SO2, or carbonyl;
34
where X is CH2, SO2, or carbonyl; and R1 and R1 are each independently selected from H, CN, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted; or
35
wherein R2 is H, (C1-C8)alkyl, or is selected from groups A above; and E is selected from groups A above;
W is (a):
36
wherein n is 2-5,
R3 is selected from H, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted;
R6 is selected from H, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted;
R4 is selected from H, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted; or is
37
where groups R10, R11 and R11 are each, independently, selected from H, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted;
R5 is H, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted, or is
38
wherein R12 and R12 are each independently selected from H, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted; or
W is (b)
39
wherein
Q is selected from the group consisting of (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C10)cycloalkyl, and (C3-C10)heterocycloalkyl; and
R7, R8, and R9 are each independently selected from H, (C1-C8)alkyl-, and phenyl(CH2), wherein said alkyl and phenyl groups are optionally substituted.
2. The compound of claim 1, wherein, independently, one or more of groups A, B, E, and Q therein consist of, or comprise, a (C6-C10)aryl group, selected from phenyl and naphthyl.
3. The compound of claim 1, wherein, independently, one or more of groups A, B, E, and Q therein consist of, or comprise, a (C1-C9)heteroaryl group, selected from furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, triazolyl, tetrazolyl, imidazolyl, 1,3,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-oxadiazolyl, 1,3,5-thiadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, pyrazolo3,4-bpyridinyl, cinnolinyl, pteridinyl, purinyl, 6,7-dihydro-5H-1pyrindinyl, benzobthiophenyl, 5, 6, 7, 8-tetrahydro-quinolin-3-yl, benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, thianaphthenyl, isothianaphthenyl, benzofuranyl, isobenzofuranyl, isoindolyl, indolyl, indolizinyl, indazolyl, isoquinolyl, quinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, and benzoxazinyl.
4. The compound of claim 1, wherein group Q therein is selected from
(a) a (C6-C10)aryl group, selected from phenyl and naphthyl;
(b) a (C1-C9)heteroaryl group, selected from furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, triazolyl, tetrazolyl, imidazolyl, 1,3,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-oxadiazolyl, 1,3,5-thiadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, pyrazolo3,4-bpyridinyl, cinnolinyl, pteridinyl, purinyl, 6,7-dihydro-5H-1pyrindinyl, benzobthiophenyl, 5, 6, 7, 8-tetrahydro-quinolin-3-yl, benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, thianaphthenyl, isothianaphthenyl, benzofuranyl, isobenzofuranyl, isoindolyl, indolyl, indolizinyl, indazolyl, isoquinolyl, quinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, and benzoxazinyl;
(c) a (C3-C10)cycloalkyl group, selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, 1,3-cyclobutadienyl, 1,3-cyclopentadienyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl, 1,4-cycloheptadienyl, 1,3,5-cycloheptatrienyl, bicyclo3.2.1octane, bicyclo 2.2.1 heptane and the norborn-2-ene unsaturated form thereof; and
(d) a (C3-C10)heterocycloalkyl group, selected from pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl, thiopyranyl, aziridinyl, oxiranyl, methylenedioxyl, chromenyl, isoxazolidinyl, 1,3-oxazolidin-3-yl, isothiazolidinyl, 1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidin-1-yl, piperidinyl, thiomorpholinyl, 1,2-tetrahydrothiazin-2-yl, 1,3-tetrahydrothiazin-3-yl, tetrahydrothiadiazinyl, morpholinyl, 1,2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, tetrahydroazepinyl, piperazinyl, and chromanyl.
5. A compound according to claim 1 selected from the group consisting of:
6-Amino-2-2-(biphenyl-4-ylmethyl)-amino-3-(1H-indol-3-yl)-propionylamino-hexanoic acid methyl ester;
2-3-(3-Fluoro-phenyl)-2-2-(toluene-4-sulfonylamino)-acetylamino-propionylamino-5-guanidino-pentanoic acid methyl ester;
6-Amino-2-2-(biphenyl-4-carbonyl)-amino-3-(1H-indol-3-yl)-propionylamino-hexanoic acid methyl ester;
2-2-(Biphenyl-4-carbonyl)-amino-3,3-diphenyl-propionylamino-5-guanidino-pentanoic acid methyl ester;
6-Amino-2-2-(biphenyl-4-carbonyl)-amino-3-(1H-indol-3-yl)-propionylamino-hexanoic acid tert-butyl ester;
6-Amino-2-2-(2-benzenesulfonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionylamino-hexanoic acid tert-butyl ester; and
6. A compound according to claim 5 selected from the group consisting of:
6-Amino-2-2-(biphenyl-4-carbonyl)-amino-3-(1H-indol-3-yl)-propionylamino-hexanoic acid tert-butyl ester; and
6-Amino-2-2-(2-benzenesulfonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionylamino-hexanoic acid tert-butyl ester.
7. A compound according to claim 1, wherein the Z group thereof has the stereospecificity
40
8. A compound according to claim 7, wherein the Z group defines an L-amino acid selected from the group consisting of L-tryptophanyl, L-histidinyl, L-3-methylhistidinyl, L-phenylalaninyl-L-diphenylalaninyl-, L-2-fluorophenylalaninyl-, L-3-fluorophenylalaninyl-, L-4-fluorophenylalaninyl-, and L-tyrosinyl-.
9. A compound according to claim 8 wherein said Z group thereof is L-tryptophanyl-.
10. A compound according to claim 1, wherein the Z group thereof has the stereospecificity
41
11. A compound according to claim 10, wherein the Z group defines an D-amino acid that is D-tryptophanyl.
12. A compound according to claim 11 wherein said Z group thereof is D-tryptophanyl-.
13. A compound according to claim 1, wherein the W group thereof has an absolute stereospecific configuration at the indicated position which corresponds to the that of the -carbon of L-amino acids.
42
14. A compound according to claim 13, wherein the W group is an L-lysine group or a (C1-C8)alkyl ester thereof, an L-ornithine group or a (C1-C8)alkyl ester thereof, an L-arginine group or a (C1-C8)alkyl ester thereof, an L-histidine group, or a (C1-C8)alkyl ester thereof, or an L-3-methylhistidine group, or a (C1-C8)alkyl ester thereof.
15. A compound according to claim 14, wherein said W group is a (C1-C8)alkyl ester of L-lysine.
16. A compound according to claim 1 wherein R1 is (C1-C8)alkyl- or phenyl(CH2) and said alkyl or phenyl group is optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
17. A compound according to claim 1 wherein R1 is (C1-C8)alkyl- or phenyl(CH2) and said alkyl or phenyl group is optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
18. A compound according to claim 1 wherein R2 is (C1-C3)alkyl-, optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
19. A compound according to claim 1 wherein R2 is (C1-C8)alkyl-, optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
20. A compound according to claim 1 wherein one or more of R3, R4, R5, and R6 is (C1-C8)alkyl- or phenyl(CH2), and said alkyl or phenyl group is optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
21. A compound according to claim 1 wherein one or more of R7, R8, and R9 is (C1-C8)alkyl- or phenyl(CH2), and said alkyl or phenyl group is optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
22. A compound according to claim 1 wherein one or more of R10, R11, and R11 is (C1-C8)alkyl- or phenyl(CH2), and said alkyl or phenyl group is optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
23. A compound according to claim 1 wherein one or more of R12 and R12 is (C1-C8)alkyl- or phenyl(CH2), and said alkyl or phenyl group is optionally substituted by one or more halo or trifluoro(C1-C8)alkyl groups.
24. A compound according to claim 1 wherein a trifluoro(C1-C8)alkyl substituent present on a B, E, R1, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R11, R12 or R12 group thereof is trifluoromethyl.
25. A pharmaceutical composition for increasing growth hormone secretion in a mammal, comprising an effective amount of a compound according to claim 1, and a pharmaceutical carrier.
26. A pharmaceutical composition for increasing secretion of gastrin or glucagon in a mammal, comprising an effective amount of a compound according to claim 1, and a pharmaceutical carrier.
27. A pharmaceutical composition for inhibiting the binding of somatostatin to the sst2 receptor therefor, comprising an effective amount of a compound according to claim 1, and a pharmaceutical carrier.
28. A method for increasing growth hormone secretion in a mammal, comprising administering an effective amount of a pharmaceutical composition according to claim 25.
29. A method for increasing secretion of gastrin or glucagon in a mammal, comprising administering an effective amount of a pharmaceutical composition according to claim 25.
30. A method for decreasing somatostatin-induced downregulation of growth hormone secretion in a mammal, comprising administering an effective amount of a pharmaceutical composition according to claim 25.
31. A pharmaceutical composition useful to cause sustained release of growth hormone in a mammal in need thereof, comprising a compound according to claim 1, and a pharmaceutical carrier.
32. A method for facilitating the sustained secretion of growth hormone in a mammal in need thereof, wherein said mammal possesses:
(a) a defect in the expression of the encoding nucleotide sequence for growth hormone, the processing of resultant mRNA, or the translation or intracellular processing and packaging of GH or precursor polypeptide thereof; or
(b) an allele of the growth hormone gene which codes for a growth hormone polypeptide that is insufficiently active;
which comprises administering an effective amount of a pharmaceutical composition according to claim 25.
33. A method for treating a human for one or more symptoms of insufficient growth hormone secretion, wherein said symptom is selected from frailty, hypoglycemia, wrinkled skin, slow skeletal growth, reduced immune function, and reduced organ function, comprising administering an effective amount of a pharmaceutical composition according to claim 25.
34. A method for treating a non-human mammal to enhance the growth and performance thereof, comprising administering an effective amount of a pharmaceutical composition according to claim 25.
35. A pharmaceutical composition according to claim 25 further comprising growth hormone releasing peptide (GHRP) or growth hormone releasing hormone (GHRH).
36. A method for increasing growth hormone secretion in a mammal, comprising administering an effective amount of a pharmaceutical composition according to claim 35.
37. A method for increasing growth hormone secretion in a mammal, comprising administering an effective amount of a pharmaceutical composition according to claim 25, and a further composition comprising growth hormone releasing peptide (GHRP) or growth hormone releasing hormone (GHRH).
38. A compound according to claim 13, wherein the W group comprises an L-diaminopimelic, L-canavanine, L-2,4-diaminobutyric, L-5-hydroxylysine, or L-epsilon-N-methyllysine group, or a (C1-C8)alkyl ester of any thereof.

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 container, comprising:
a mouth;
a wall section which adjoins the mouth in a longitudinal direction of the container; and
a base section, wherein the wall section merges into the base section and the container is formed in one piece, the base section comprising:
an injection point located in an interior region of the base section;
a central region which surrounds the injection point in a radial direction with respect to the longitudinal direction;
a plurality of curved outer ridges which extend from the central region to the wall section, and have a non-zero curvature continuously therebetween, said curved outer ridges each having a point of inflection, wherein a portion of each curved outer ridge between said central region and said point of inflection comprises a continuously changing curvature; and
a plurality of depressed regions which extend from the central region to the wall section and which are disposed between ones of said plurality of curved outer ridges, each of said depressed regions having a constant radius of curvature in at least one respective radial direction of the container.
2. The container according to claim 1, wherein the base section is designed with point symmetry with respect to the injection point.
3. The container according to claim 1, wherein the central region, with respect to a geometric centre point of the base section, has a radius of less than 15 mm.
4. The container according to claim 1, wherein the curved outer ridges each have a first curved region with a substantially constant first radius of curvature (R1).
5. The container according to claim 4, wherein the first curved region is adjoined on the radially outer side by a second curved region, wherein this second curved region likewise has a substantially constant second radius of curvature (R2).
6. The container according to claim 5, wherein the first curved region and the second curved region are curved in a same direction.
7. The container according to claim 5, wherein the second radius of curvature (R2) of the second curved region is greater than the first radius of curvature (R1) of the first curved region.
8. The container according to claim 1, wherein the base section is a free-formed base section.
9. The container according to claim 1, wherein the container has a liquid capacity of at least 250 ml.